Pancreatic hormone linked with severe heart disease in obese and diabetic patients

February 16, 2012, University of California - Davis

Severe heart damage in people who are obese and diabetic is linked with a pancreatic hormone called amylin, UC Davis researchers have found.

In the failing hearts of patients who were obese and diabetic, the scientists discovered strings of proteins, small fibers and plaques made of amylin, the hormone that produces the feeling of being full after eating. They also showed in an that amylin accumulation in the heart leads to heart muscle destruction and failure.

Published in the February 17 issue of the journal , the study also found amylin buildup in who are not obese, suggesting the potentially dangerous accumulations may start before a diabetes diagnosis.

is the number-one killer in obese and diabetic populations. Controlling the circulation of amylin hormone in the blood might lessen or prevent disabilities and deaths from , the scientists said.

"Amylin appears to be a stealth killer," said Florin Despa, an assistant professor of pharmacology at UC Davis and senior author of the study. "There is only one amylin protein for every 100 insulin proteins in the blood, so it has been under the radar until recently."

In healthy people, amylin circulates in the blood together with --the hormone that controls carbohydrate and fat metabolism -- and principally regulates gastric fluxes and the sensation of satiety.

In studies of both normal and failing donated hearts of people undergoing heart-transplant surgery, the researchers found little or no amylin accumulation in lean people. But a quite different picture emerged from examinations of of obese and type 2 diabetic patients. In failing hearts of these patients, they found extensive accumulation of amylin in strings of 10 to 20 proteins called oligomers. They detected a smaller but still abnormal buildup in nonfailing hearts from patients who were overweight but not obese.

Using genetically engineered rats that secrete human amylin in the same proportion as it is found in obese people, the researchers determined that amylin oligomers attach to membranes of myocytes -- the heart-muscle cells that control heart beats. This made the membranes more porous to calcium, which changed myocyte contractility, altered the expression of vital proteins and, eventually, caused cells to die.

"The significantly altered cardiac myocyte structure and function in the rats, along with the high levels of oligomers in the human heart tissue, strongly suggest that amylin is a major contributor to heart failure in obese and ," Despa said.

Despa thinks that the link between cardiac amylin accumulation and heart disease has been overlooked because amylin circulates in relatively small amounts in blood, and because animals, including rats, that are often used in most studies of diabetic cardiac dysfunction do not normally express the form of amylin that aggregates and builds up in tissues.

The scientists now hope to find ways to curb amylin buildup in the heart before it has the chance to destroy muscle tissue.

"Drugs that block amylin from forming into toxic oligomers could significantly reduce the chances of heart failure," Despa said.

For the research, amylin protein accumulation was detected in human and rat heart tissues and cell cultures using immunohistochemistry, immunofluorescence and Western blot. Heart dysfunction in the rats was identified by studying the physiological performance of isolated myocytes and by measuring the expression of tell-tale proteins that deform cardiac muscle. The researchers used echocardiography and measurements of blood flow to assess heart tissue structure and performance and changes in myocardium contractions.

Explore further: Preventing diabetes damage: Zinc's effects on a kinky, two-faced cohort

Related Stories

Preventing diabetes damage: Zinc's effects on a kinky, two-faced cohort

June 30, 2011
In type 2 diabetes, a protein called amylin forms dense clumps that shut down insulin-producing cells, wreaking havoc on the control of blood sugar. But zinc has a knack for preventing amylin from misbehaving.

Amylin's long-delayed diabetes drug gets FDA nod

January 28, 2012
Amylin Pharmaceuticals won approval Friday for its long-delayed diabetes drug Bydureon, a next-generation treatment that requires fewer injections than the company's 7-year old diabetes medicine, Byetta.

In the pursuit of dangerous clumps

July 28, 2011
When normal proteins form protein clumps in the body, then alarm bells start ringing. Such clumps, called "amyloids," are closely associated with Alzheimer's disease and type 2 diabetes, formerly called adult-onset diabetes. ...

Recommended for you

Starting periods before age of 12 linked to heightened risk of heart disease and stroke

January 15, 2018
Starting periods early—before the age of 12—is linked to a heightened risk of heart disease and stroke in later life, suggests an analysis of data from the UK Biobank study, published online in the journal Heart.

'Decorated' stem cells could offer targeted heart repair

January 10, 2018
Although cardiac stem cell therapy is a promising treatment for heart attack patients, directing the cells to the site of an injury - and getting them to stay there - remains challenging. In a new pilot study using an animal ...

Exercise is good for the heart, high blood pressure is bad—researchers find out why

January 10, 2018
When the heart is put under stress during exercise, it is considered healthy. Yet stress due to high blood pressure is bad for the heart. Why? And is this always the case? Researchers of the German Centre for Cardiovascular ...

Two simple tests could help to pinpoint cause of stroke

January 10, 2018
Detecting the cause of the deadliest form of stroke could be improved by a simple blood test added alongside a routine brain scan, research suggests.

Heart-muscle patches made with human cells improve heart attack recovery

January 10, 2018
Large, human cardiac-muscle patches created in the lab have been tested, for the first time, on large animals in a heart attack model. This clinically relevant approach showed that the patches significantly improved recovery ...

Place of residence linked to heart failure risk

January 9, 2018
Location. Location. Location.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.